Note: Counseling and informed consent are recommended for genetic testing. A consent form is available as a resource.

INTERPRETATIVE DATA:

Incidence: 1 in 100,000. About 6% of autosomal dominant ataxias.

Inheritance: Autosomal dominant. Variable age of onset but complete penetrance.

Disease Characteristics:

In individuals with molecularly confirmed ATXN1 there is progressive cerebellar ataxia, dysarthria, and eventual deterioration of bulbar functions. Early symptoms include gait disturbance, slurred speech, and difficulty with balance. Symptoms progress to include development of up-gaze palsy, dysdiadochokinesia, and hypotonia. In advanced stages, muscle atrophy, cognitive impairment, chorea, dystonia, and bulbar dysfunction are seen. Once the involuntary neurological symptoms start affecting autonomic muscle systems death occurs rapidly. The size of the CAG repeat region dictates the age of onset and the speed of the progression of symptoms rather than the actual spectrum of symptoms.

Molecular Genetic Mechanism: A neurodegenerative disorder that demonstrates the genetic anticipation characteristic of an unstable expansion of CAG trinucleotide repeats within the coding region of the ATXN1 gene. This glutamine repeat region is found to be polymorphic in the normal population with sizes ranging from 6 to 44 repeats. Pathogenicity of alleles in the 36 to 44 repeat range depends on the presence of CAT repeat interruption; those without the CAT interruptions will be considered either mutable normal for 36 to 38 CAG repeats or fully penetrant for 39 to 44 CAG repeats. Alleles of more than 39 Uninterrupted CAG repeats and over 45 repeats are considered abnormal. The age of onset and increase of CAG size often increases each generation (Anticipation).

Test Limitations: This test examines the CAG repeat regions, exclusively. However, no other mechanism has been described for SCA1 and the test is considered diagnostic. Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete. Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms.

INDICATIONS FOR USE:

Individuals with a family history of SCA1 who want to determine their true risk.